Multi-chiral materials comprising metallosupramolecular and covalent helical polymers containing five axial motifs within a helix

Supramolecular and covalent polymers share multiple structural effects such as communication mechanisms among monomer repeating units, which are related to their axial helical structure. Herein, a unique multi-helical material combining information from both metallosupramolecular and covalent helical polymers is presented. In this system, the helical structure described by the poly(acetylene) (PA) backbone (cis-cisoidal, cis-transoidal) guides the pendant groups in a fashion where a tilting degree emerges between a pendant and the adjacent ones. As a result, a multi-chiral material is formed comprising four or five axial motifs when the polyene skeleton adopts either a cis-transoidal or cis-cisoidal configuration: the two coaxial helices—internal and external—and the two or three chiral axial motifs described by the bispyridyldichlorido PtII complex array. These results show that complex multi-chiral materials can be obtained by polymerizing appropriate monomers that combine both point chirality and the ability to generate chiral supramolecular assemblies.

phenyleneethynylene) (OPE) groups used as spacers 61 . As a result, a POPEPA can adopt a multi-helical scaffold where four different axial motifs coexist in the helical material: the two coaxial helices-internal (helix 1) and external (helix 2)-and the two helices described by the OPE axial array (helices 3 and 4) 61 .
Herein, using rational monomer design, we have achieved unique multi-helical materials that exist in up to five helical conformations. To this end, we selected a metal-containing monomer, consisting of an asymmetric bispyridyldichlorido Pt(II) complex, functionalized on one edge with a polymerizable terminal alkyne and with a chiral group on the other edge to induce a screw sense in the helical polymer. The choice of the Pt(II) center is biased by the versatile self-assembly behavior and interesting photophysical properties of metal-based monomers [62][63][64][65][66] . Particularly, bispyridyldichlorido Pt(II) complexes with an extended aromatic surface are privileged scaffolds to prepare a large variety of supramolecular structures by different aggregation pathways and multiple weak non-covalent interactions [67][68][69][70][71][72] . Hence, an asymmetric bispyridyldichlorido Pt(II) complex should meet all the requirements to generate a multi-helical scaffold.

Results
To validate our hypothesis, two different pyridine ligands, one containing either a chiral L-valine or an L-alanine methyl ester residue, and another one bearing a 4-alkynyl group were synthesized and complexed with a Pt(MeCN) 2 Tables 1-4). The terminal alkyne group enables the further polymerization of mono-(S)-1 and mono-(S)−2 using [Rh(nbd) Cl] 2 as catalyst (nbd = 2,5-norbornadiene) to obtain poly-(S)−1 and poly-(S)−2, in good yield and high content of cis-double bonds (Fig. 1).
UV-vis studies of mono-(S)-1 and mono-(S)-2 show spectra with four bands between 350 and 250 nm (vide infra). UV-vis theoretical calculations for mono-(S)-1 (time-dependent density functional theory) (TD-DFT) together with either rCAM-B3LYP and wB97XD density functional and LANL2DZ basis set [TD-DFT(wB97XD)/LANL2DZ), TD-DFT(rCAM-B3LYP)/LANL2DZ)], were performed on the molecular structure obtained after DFT optimization (see Supplementary Figs. 18,19). Both theoretical calculations show a good match between the experimental and the calculated ECD trace, being slightly better when the functional wB97XD is used. From the TD-DFT (wB97XD)/ LANL2DZ theoretical studies, we identified which fragments of mono-(S)-1 are responsible for these absorption bands. Thus, the UV-band at higher wavelength-ca. 345 nm-corresponds to MLCT involving the core of the bispyridyldichlorido Pt(II) complexes, the band at ca. 305 nm corresponds to the para-ethynylpyridyl moiety, while the band at 280 nm is attributed to the para-pyridylbenzamide of (L)-valinemethyl ester complexed to the Pt(II) ion. Finally, the band at 250 nm is assigned to the benzamide group of the chiral moiety (See Fig. 1c and Supplementary Figs. 18,19).
Intriguingly, UV-vis studies of poly-(S)-1 and poly-(S)-2 show an interesting phenomenon. Thus, while in moderately polar solvents such as THF or DCM, poly-(S)-1 adopts a stretched helix (cistransoidal), in more polar solvents such as DMF, the polymer adopts a compressed scaffold (cis-cisoidal). This change in elongation is explained by the hypsochromic shift experienced by the polyene band (from 417 to 380 nm) when comparing a DCM/THF solution to a DMF one. In the case of poly-(S)-2, similar results are obtained in DMF, whereas the experiments in THF or DCM were not possible due to insufficient solubility. The compression of the polyene backbone is accompanied by a color change from yellow to translucent due to the lack of alternating double bond conjugation of the polyene backbone (Fig. 2a). Note that the lack of emission, i.e. MMLCT luminescence, both in DMF and DCM (see Supplementary Fig. 14) indicates the absence of short Pt-Pt interactions in the polymers [68][69][70][71] .
ECD studies of poly-(S)-1 and poly-(S)-2 in these solvents show again an interesting effect. Thus, poly-(S)-1 shows a complex ECD spectra in THF or DCM, with multiple bands in the 250-350 nm region (Fig. 2b). On the contrary, in polar solvents such as DMF, the ECD   spectrum is dominated by a strong bisignate in the 250-350 nm region (Fig. 2c). Careful inspection of the ECD spectrum of poly-(S)-1 in DMF reveals that the first negative Cotton band shows two minima, one centered at 385 nm and the other at 355 nm, which corresponds to the polyene backbone and the core of the Pt(II) complex, respectively (see above). Moreover, a strong positive Cotton band is obtained at 302 nm, and a negative one at 280 nm. More precisely, the band at ca. 302 nm corresponds to the para-ethynylpyridyl moiety, while the band at 280 nm is attributed to the para-pyridylbenzamide of (L)-valinemethyl ester, as previously discussed in the monomer calculations (Fig. 1c). The complexity of the ECD spectrum obtained for poly-(S)-1 in different solvents can be explained by combining the classical ECD spectrum of a poly(phenylacetylene) (PPA), which presents three alternating Cotton bands, in this case −/+/−, with the ECD trace obtained by a chiral supramolecular orientation of the metal containing spacers within the helical scaffold. Thus, while in DMF, poly-(S)-1 adopts a compressed cis-cisoidal structure (ω 1 < 90°), in DCM or THF an elongated cis-transoidal structure (ω 1 > 90°) is adopted by the polyene backbone. As a result, two different architectures with different structural properties are obtained for poly-(S)-1. The cis-cisoidal helix in PPAs is made by two coaxial helices that rotate in the same direction (P int /P ext or M int /M ext ), while the cis-transoidal helix rotates in the opposite direction (P int /M ext or M int /P ext ). Moreover, in the cisoidal scaffold, the helix contains three residues per turn, generating a helix with three crests at the periphery. For the transoidal scaffold, the helix possesses two residues per turn, describing a helix with two crests (Fig. 2d).
Interestingly, looking at the arrangement of the metal-containing spacers on the different crests of the cis-cisoidal and cis-transoidal helices, it is possible to create a unique helical arrangement of these achiral spacers within the helix crest whose sense depends on the helical scaffold. Accordingly, in cis-cisoidal PAs, the orientation of the achiral spacers within the helix crest exhibits the same sense as the internal and external helices. As a result, a multi-helical structure with five structural motifs is generated-internal helix, external helix and three helices described by the arrangement of the metal containing spacers at the helix crest.
From the literature, it is known that PPAs with a P orientation of the polyene backbone show an alternating ECD spectrum with three Cotton bands +/−/+, while those PPAs with an M orientation of the polyene backbone show the opposite orientation of the ECD bands (−/+/−). To determine how the axially chiral orientation of the metal containing monomer affects the spectrum, theoretical ECD studies were carried out in a supramolecular helical arrangement of an asymmetric bispyridyldichlorido Pt(II) complex. To this end, the geometry of supramolecular trimers arranged as left-handed and righthanded helices was optimized using DFT together with the rCAM-B3LYP functional and the LANL2DZ basis set [73][74][75][76][77][78][79][80] . In this case, the wB97XD functional was not employed considering the resemblance between the theoretical UV-vis obtained for the theoretical studies of (S)-1, and the computation time needed for the wB97XD functional.
Considering this result, if the polymer adopts a cis-transoidal scaffold with a preferred P orientation of the polyene backbone, the external helix and the axial array described by the metal-containing spacer will rotate in opposite direction (M helix). Thus, while the polyene produces a +/−/+ ECD trace, the axial array of the spacers promotes a −/+ ECD with an opposite orientation to that described by the polyene. As a result, depending on the intensity and wavelength absorbance of the first and second ECD bands produced by the polyene backbone and the axial array of the metal-containing spacer, complex ECD spectra are obtained with multiple positive and negative ECD bands as observed in poly-(S)-1 dissolved in DCM or THF (Fig. 2b).
On the contrary, in a cis-cisoidal helix with a P orientation of the internal and the external helices, and a P orientation of the asymmetric Pt(II) complexes used as spacers, the first and second cotton bands of the classical ECD spectrum (+/−/+) experience an additive effect of the (+/−) bands obtained for the axial array of the spacers.
As a result, an ECD spectrum with three alternating Cotton bands is obtained, where the second is very intense.
In the case of a polymer adopting a cis-cisoidal structure with a preferred M screw sense of the polyene backbone, the opposite −/+/− ECD trace must be obtained. This is in fact the ECD pattern that we observed for poly-(S)-1 dissolved in DMF: three alternating Cotton bands (−/+/−), showing the second and third band an abnormally large intensity, confirming the additive effect by ECD theoretical calculations (TD-DFT(CAM-B3LYP)/LANL2DZ). Analogous spectra were obtained for poly-(S)-2 dissolved in DMF (Fig. 3b and Supplementary  Information).
VT-ECD studies of poly-(S)-1 in THF and DMF corroborate these structures, showing for poly-(S)-1 in DMF a large thermal stability (above 80°C) promoted by the three axial arrays of the asymmetric Pt(II) complexes used as spacers. Thermal studies for poly-(S)-1 in THF disclose a lower thermal stability due to the presence of just two axial arrays of the asymmetric bispyridyldichlorido Pt(II) complexes used as spacers within the helical scaffold.

Discussion
In summary, we have achieved through two different examples-poly-(S)-1 and poly-(S)-2-unique multi-helical materials built from a supramolecular helix, made from a bispyridyldichlorido Pt(II) complex and a covalent helical polymer (PA). When poly-(S)-1 is dissolved in solvents of moderate polarity, e.g. THF, the polyene backbone adopts a cistransoidal helical scaffold with four axial motifs: the internal helix (helix 1) described by the polyene backbone, the external helix (helix 2) described by the pendants and two helices described by the bispyridyldichlorido Pt II complexes used as spacers (helices 3 and 4). These four axial motifs are interconnected describing either a M 1 /P 2 /P 3 /P 4 or P 1 /M 2 /M 3 /M 4 multi-axial chiral system. Interestingly, an additional axial motif emerges when the polymer is dissolved in polar solvents such as DMF. In such case, poly-(S)-1 adopts a cis-cisoidal scaffold that shows five axial motifs: the internal helix (helix 1), the external helix (helix 2), and axial motifs described by the bispyridyldichlorido Pt II complexes used as spacers (helices 3 and 4). These structural motifs are interconnected describing either a P 1 /P 2 /P 3 /P 4 /P 5 or M 1 /M 2 /M 3 /M 4 /M 5 multiaxial chiral material. These results indicate that rational molecular design can be exploited to stabilize supramolecular helices in covalent polymers, which paves the way for the design of complex multi-helical materials.

Methods
CD measurements were performed on a Jasco-720 and VT-CD measurements on a Jasco-1500 with a 1 mm quartz cuvette. The amount of polymer used for CD and VT-CD measurements was 0.6 mg/mL. UV spectra were registered on a Jasco V-750 with a 1 mm quartz cuvette. The amount of polymer used for UV measurements was 0.6 mg/mL.
Optical rotation was measured on a Jasco-P2000. Mass spectra were obtained on an HP 5988A spectrometer (Hewlett-Packard, Palo Alto, CA, USA).
Elemental analyses were recorded using a Foss-Heraeus CHNO-Rapid analyzer.
Raman spectra were performed on a Renishaw confocal Raman spectrometer (Invia Reflex model), equipped with two lasers (diode laser 785 nm and Ar laser 514 nm).
DSC traces were obtained on a DSC Q200 Tzero Technology (TA Instruments, New Castle, UK), equipped with a refrigerated cooling system RCS90 (TA Instruments, New Castle, UK), using a Tzero lowmass aluminum pan.
TGA traces were obtained on a TGA Q5000 (TA Instruments, New Castle, UK) using a platinum pan.
Photoluminescence spectra were obtained on a Horiba Fluoromax-Plus-C fluorimeter using a 10 mm quartz cuvette.
IR spectra were obtained on a JASCO-FTIR-6800. IR spectra in solution were recorded using a CaF2 cell with a path length of 0.1 mm.
Computational studies: 3D structures were done with the software package Spartan´18. The asymmetric bispyridyldichlorido Pt(II) complex was built by using the data obtained from another bispyridyldichlorido Pt(II) complex (CCDC deposit number 2004415). Timedependent density functional theory (TD-DFT) together with either rCAM-B3LYP and wB97XD density functional and LANL2DZ basis set [TD-DFT(wB97XD)/LANL2DZ), TD-DFT(rCAM-B3LYP)/LANL2DZ)] were carried out with the software package Gaussian 16, rev C.01.   three times with HCl 1 M and a saturated solution of NaHCO 3 . The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered and evaporated at reduced pressure. The crude product was chromatographed on silica gel with pentane/ethyl acetate (70:30) as eluent (388 mg, 55 % of yield).

General protocol for complexation and deprotection of monomers
Ligand 3 (1.7 equiv.), trans-PtCl 2 (PhCN) 2 (1.35 equiv.) and the corresponding ligand 1 or 2 (1 equiv.) were placed in a pressure tube and subjected to five vacuum/Ar cycles. Subsequently, dry and degassed toluene was added and the mixture was heated to 70°C and stirred at this temperature for one week. After evaporating the solvent, the crude was chromatographed on silica gel with pentane/ethyl acetate (80:20) as eluent.
The corresponding Pt(II) complexes with the protected alkyne were dissolved in a mixture of THF:MeOH (3:1). Next K 2 CO 3 was added (1.20 equiv.) and the reaction was stirred at r.t. for 1 h. The crude was chromatographed on silica gel with pentane/ethyl acetate (60:40) as eluent.

Synthesis of polymers
The reaction flask (sealed ampoule) was dried under vacuum and argon flushed for three times before monomer was added as a solid. Dry THF was added with a syringe. Next, a solution of rhodium norbornadiene chloride dimer, [Rh(nbd)Cl] 2 , and Et 3 N in dry THF was added to the reaction under stirring at 30°C. After 6 h, the resulting polymer was diluted in CH 2 Cl 2 and precipitated in methanol and centrifuged twice. Next, the polymer was reprecipitated in hexane and centrifuged again.

Data availability
All data is available from the corresponding authors upon request.